UBA5: Ubiquitin-Like Modifier Activating Enzyme 5
A critical enzyme in UFMylation, linked to neurodevelopmental disorders and cancer
Gene Information Card
| Symbol | UBA5 |
|---|---|
| Full Name | Ubiquitin-like modifier activating enzyme 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q22.1 |
| NCBI Gene ID | 79876 ncbi.nlm.nih.gov/gene/79876 |
| Ensembl ID | ENSG00000145908 |
| UniProt ID | Q9GZZ9 |
| OMIM ID | 610553 |
| HGNC ID | 23260 |
| Aliases | UFM1-activating enzyme, UBA5_HUMAN |
Description
UBA5 encodes the ubiquitin-like modifier activating enzyme 5, which specifically activates UFM1 (ubiquitin-fold modifier 1) through an ATP-dependent mechanism. This activation is the first step in the UFMylation pathway, a post-translational modification process involved in endoplasmic reticulum homeostasis, hematopoiesis, and cellular stress responses. Mutations in UBA5 cause autosomal recessive neurodevelopmental disorder with cerebellar atrophy and epilepsy (NEDCAE).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with cerebellar atrophy and epilepsy (NEDCAE) | Loss-of-function mutations impair UFM1 activation, disrupting UFMylation and leading to neuronal dysfunction and cerebellar degeneration. | ClinVar, OMIM |
| Epileptic encephalopathy, early infantile | Biallelic UBA5 variants reduce enzyme activity, affecting neuronal development and synaptic function. | ClinVar, OMIM |
| Hypomyelinating leukodystrophy | Defective UFMylation due to UBA5 mutations impairs myelin formation and maintenance. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Cerebellum | 15.1 | Medium |
| Heart | 8.5 | Low |
| Liver | 6.2 | Low |
| Kidney | 7.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.5 | Neuronal model |
| HEK293 (embryonic kidney) | 9.8 | Common expression system |
| HeLa (cervical carcinoma) | 8.2 | Epithelial model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1111G>A (p.Ala371Thr) | Missense | Rare | Reduced UFM1 activation; associated with NEDCAE |
| c.329A>G (p.Tyr110Cys) | Missense | Rare | Impaired ATP binding; loss of function |
| c.904C>T (p.Arg302*) | Nonsense | Very rare | Premature truncation; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Most UBA5 disease-associated mutations are loss-of-function, reducing or abolishing UFM1 activation.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • UFM1 activating enzyme activity (GO:0019789) | • ATP binding (GO:0005524) |
| • UFMylation (GO:0071569) | • protein modification by small protein conjugation (GO:0032446) |
Pathways
• UFMylation pathway (Reactome: R-HSA-8866654)
• Protein modification by UFM1 (KEGG: hsa04120)
Protein Summary
UBA5 is a 404-amino acid protein that functions as the E1-like activating enzyme for UFM1. It catalyzes the ATP-dependent adenylation of UFM1, forming a UFM1-AMP intermediate, followed by transfer to its catalytic cysteine residue. This activated UFM1 is then transferred to the E2-like conjugating enzyme UFC1. UBA5 is essential for cellular stress responses, particularly under endoplasmic reticulum stress, and is highly expressed in brain tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UBA5 Knockout HEK293 Cell Line | EDJ-KQ12033 | Human | 79876 | Details Get a Quote |
| UBA5 Knockout A-549 Cell Line | EDJ-KQ40648 | Human | 79876 | Details Get a Quote |
| UBA5 Knockout HCT 116 Cell Line | EDJ-KQ40649 | Human | 79876 | Details Get a Quote |
| UBA5 Knockout HeLa Cell Line | EDJ-KQ40650 | Human | 79876 | Details Get a Quote |
